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Full text of "United States Navy Medical News Letter Vol. 32 No. 3, 1 August 1958"

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NavMed 369 


rara- ' ra-y-tt-ww;-:- 

:.':': ;.:' 

Rear Admiral Bartholomew W. Hogan MC USN 
Captain Leslie B. Marshall MC USN (RET) 

- Surgeon General 

Vol. 32 Friday, 1 August 1958 

No. 3 


Historical Fund of the Navy Medical Department 2 

Mass Prophylaxis of Epidemic Streptococcal Infections 3 

Syndrome of Mineralocortocoid Excess 6 

Osmotic Diuretic Treatment of Refractory Edema 8 

Myelo scintigraphy . . . . . . 11 

Cardiac Rehabilitation 12 

Iron as a Therapeutic Agent in Pediatric Practice . 14 

Sarcoma of the Mammary Gland . 16 

Promethazine as an Adjunct to Obstetrical Analgesia and Sedation 18 

Occupational Medicine Program - Scientific Assembly of AMA 20 

Expired Air Resuscitation 22 

Seminar in Aviation Medicine 23 

Environmental Sanitation Course 24 

MSC Training in Navy Management 25 

From the Note Book 25 

Ristocetin - Effects and Side Effects 27 


Erroneous Submission of Supplement to Dental Service Report 29 

Casualty Treatment Training to be Exhibited in Brussels 29 


Credit for Attending Professional Meetings 29 

Medical Ensign USNR Designator Changed 30 

Contingency Option Act and Aid to Dependents 31 


17th VA-AF Conference on Chemotherapy of Tuberculosis . 31 

Medical News Letter, Vol. 32, No. 3 

of the 

A committee has been formed with representation from the Medical 
Corps, Dental Corps, Medical Service Corps, Nurse Corps, and 
Hospital Corps for the purpose of creating a fund to be used for the 
collection and maintenance of items of historical interest to the Medical 
Department. Such items will include, but will not be limited to, por- 
traits, memorials, etc., designed to perpetuate the memory of dis- 
tinguished members of the Navy Medical Department. These memorials 
will be displayed in the Bureau of Medicine and Surgery and at the 
National Naval Medical Center. Medical Department officers, active 
and inactive, are invited to make small contributions to the fund. It 
is emphasized that all donations must be on a strictly voluntary basis. 
Funds received will be deposited in a Washington, D. C. bank to the 
credit of the Navy Medical Department Historical Fund, and will be 
expended only as approved by the Committee or its successor and for 
the objectives stated. 

It is anticipated that an historical committee will be organized at each 
of our medical activities. If you desire to contribute please do so 
through your local historical committee or send your check direct, 
payable to Navy Medical Department Historical Fund, and mail to; 

Treasurer, N. M. D. Historical Fund 
Bureau of Medicine and Surgery (Code 14) 
Department of the Navy 
Washington 25, D. C. 


F. P. GILMORE, Rear Admiral (MC) USN, Chairman 
R. W. MALONE, Rear Admiral (DC) USN 
W. C. CALKINS, Captain (MSC) USN 
R. A. HOUGHTON, Captain (NC) USN 
T. J. HICKEY, Secretary-Treasurer 

Medical News Letter, Vol. 32, No. 3 

Mass Prophylaxis of Epidemic Streptococcal Infections 

Experience at a Naval Training Center - 

Winter 1956-57 

The most recent of the Navy Medical Department's continuing studies 
on practical and effective methods of controlling epidemic streptococcal 
infections in recruit populations is reported. The method of prophylactic 
intramuscular injection of benzathine penicillin G for this purpose was a 
direct outgrowth of the studies done at the same station in a previous win- 
ter by Schreier, et al. 

Starting in December, when the prevalence of streptococcal infections 
began to increase, Schreier and his co-workers administered 600, 000 units 
of benzathine penicillin G to all new recruits within a few days after their 
arrival at the station. Experience had shown that during most epidemics 
a large percentage of streptococcal infections were acquired in the first 
month of the training period. Administration of benzathine penicillin at the 
beginning of training theoretically offered almost complete protection for 
the first half of the training period. 

In the current study, it was decided to employ the same dose of ben- 
zathine penicillin, but to administer it during the fourth instead of the first 
week of training. By this change, it was hoped that adequate therapy could 
be provided for such infections as had occurred before the injection and 
that protection from new infection would be provided between the fourth and 
eighth weeks of the 10-week period of training. In this way, only in the last 
2 weeks would a recruit lack some protection against development of rheu- 
matic fever if epidemic streptococcal infections occurred during the winter. 
It was further decided to administer a larger dose of benzathine penicillin G 
to a part of the population because the longer period of protection supposedly 
afforded by 1, 200, 000 units would further reduce the unprotected period at 
the end of training and comparative data were desired on the duration of 

The program of streptococcal prophylaxis was carried out on the male 
recruit population at the United States Naval Training Center, Bainbridge, 
Md. , from October 29, 1956 to May 9, 1957. 

A Navy recruit receives approximately 70 days of training. The first 
week consists mainly of processing and indoctrination during which recruits 
are grouped into companies of 96 men. The company remains nearly intact 
during the remaining 9 weeks of scheduled training which includes class- 
room work, physical conditioning, and military drill. Men in the company 
share a large dormitory, attend classes and meals together, and are other- 
wise in close contact with each other throughout training. A small number 
of men are set back into another company as a result of academic failure, 
illness, or disciplinary action. These men are often on the station for 
much longer than 70 days. 

4 Medical News Letter, Vol. 32, No. 3 

During the study, all new recruits except those who reported a definite 
history of previous reaction to penicillin were given an injection of ben- 
zathine penicillin during the fourth week of training, approximately 22 to 28 
days after arrival at the station. A total of 12,858 men received an injec- 
tion and 237 (1. 8%) were excused because of a history of allergy to penicil- 
lin. Men in each company not giving a history of reaction to penicillin were 
divided into two groups by the last digit of the service number. Those with 
even numbers were given 600, 000 units of benzathine penicillin intramus- 
cularly, and those with odd numbers were given 1,200, 000 units. 

The incidence of streptococaal disease and, more particularly rheu- 
matic fever, during the winter of 1956-57 was the lowest in the history of 
this station which had a longstanding reputation for its annual epidemics. 

The exact role that the prophylactic program played in this low inci- 
dence is difficult to define. In a mass prophylactic program designed to 
protect the entire population, controls are impossible. If any large group 
had been left untreated and incurred a considerable amount of streptococcal 
disease, the degree of stress to which the treated population would have been 
subjected would have been increased. As a result, more infections "break- 
ing through" penicillin protection might occur among the treated group and 
give an erroneous impression of what could be achieved by a given dose of 
penicillin under conditions of lesser stress. On the other hand, a small 
control group of untreated recruits would probably have had less strepto- 
coccal disease than might normally have occurred because the majority of 
the population were protected and the degree of exposure or stress markedly 
reduced. When the control group influences the treated group, or the treated 
group the control in this fashion, a controlled study is obviously impracti- 

Because controlled studies cannot be carried out, the evaluation of a 
mass prophylactic program of the type employed must depend on repeated 
experience over a number of years, even though the experience in one winter 
is not strictly comparable to that of another winter. Some idea of the value 
of the current program can be gained by comparison with past experience 
in recruits at the same station. The results of the program employed by 
Schreier, et al. in the previous winter were thought to have been good, and 
the 27 cases of rheumatic fever that occurred were the lowest total for any 
winter in the past. When compared with that record, however, the occur- 
rence of only 3 cases of rheumatic fever in the current winter constituted 
a remarkable record. The difference is far in excess of anything that 
might be attributed to the decrease in population at risk during the current 
study (20,000 including recruits on the station at the beginning and end of 
the study who were not treated) when compared to that at risk in the former 
study (30,000). 

In comparison with the previous year, it appears that delaying the 
prophylactic injection had the effect of doubling the protection afforded by 

Medical News Letter, Vol. 32, No. 3 

a single injection. Undoubtedly, 4 weeks' delay would have been too long if 
there had been more streptococcal disease in the population at the beginning 
of the program. In that instance, more infections would probably have oc- 
curred in the first 2 weeks of training, and eradication of the organism after 
the longer interval might well not have prevented rheumatic fever from occur- 

Complete definition of the degree and duration of protection afforded 
by the two doses is not a simple problem. Preparations that appear to have 
about equal capabilities under conditions of stress prevailing when strep- 
tococcal infections are spreading slowly and sporadically may vary widely 
when the conditions of stress are those prevailing during an epidemic. The 
comparison in this study is, therefore, applicable only where the degree of 
stress is not very marked. 

Infections broke through penicillin protection with equal frequency and 
at about the same intervals after injection of the two dosages of benzathine 
penicillin used. If — as has been commonly believed — the larger dose provides 
more complete and longer protection against streptococcal infection, it was 
not evident under the conditions of study. The data of Davis, et al. on the 
use of 900,000 units prophylactically are very similar to those obtained in 
this study if the populations at risk and degree of exposure to untreated popu- 
lations are taken into account. These data further affirm the impression 
that a larger dose of benzathine penicillin does not necessarily increase the 
degree of protection afforded within the first 30 days after injection and 
cast some doubt on the validity of data considered by the American Heart 
Association in increasing the recommended dosage for patients receiving 
continuous prophylaxis against recurrent rheumatic fever from 600,000 units 
monthly to 1, ZOO, 000 units. 

Numerous prophylactic studies of the past have indicated clearly that 
streptococcal infections and rheumatic fever could be completely prevented 
if enough penicillin is used at sufficiently frequent intervals. From a prac- 
tical standpoint, however, the stopping place seems to be the point at which 
the medical problems created by reactions to penicillin begin to exceed the 
problems caused by streptococcal infections and their complications or 
sequelae. Under the present conditions of training Navy recruits at this 
station, it appears that the method of prophylaxis employed in the current 
study has afforded the maximum reduction in streptococcal infections that 
it will prove practicable to seek. Although reactions to penicillin were not 
a particular problem, any increase in the amount of penicillin might well 
create the condition under which reactions are more frequent than strepto- 
coccal infections. (McFarland, R. B. , M. D. , Captain Colvin, V. G. , MC USN, 
Captain John R. Seal MC USN, Mass Prophylaxis of Epidemic Streptococcal 
Infections with Benzathine Penicillin G: New England J. Med. , 258 : 1277-1283 
June 26, 1958) 


Medical News Letter, Vol. 32, No. 3 

The Syndrome of Mineralocortocoid Excess 

The effect of acute potassium deficiency on neuromuscular transmis - 
sion and cardiac action is readily recognized and can be promptly repaired 
by administration of potassium salts. The consequences of longstanding 
potassium depletion — including both functional and anatomical changes in 
kidneys, heart, and muscle — are not so generally appreciated. Chronic 
depletion of potassium follows prolonged inability to ingest and absorb 
dietary potassium or loss through persistent diarrhea or abuse of laxatives. 
Potassium may be lost in urine because of disease involving the renal tub- 
ules or during dehydration, acidosis, or other disorders which impair 
normal renal conservation of potassium. Excessive "mineralocorticoid" 
action, due to increased secretion by the adrenal cortex or to exogenous 
corticosteroids, leads to potassium depletion with specific features which 
distinguish it from other forms of potassium loss. 

When large doses of a typical mineralocorticoid, desoxycorticoster- 
one, are given to patients without adrenals, sodium and water excretion 
are reduced, weight rises as extracellular fluid is accumulated; if over- 
dosage is continued, edema increases to anasarca with signs resembling 
congestive cardiac failure. In normal man, however, large doses of desoxy- 
corticosterone are followed by only minor increases in body weight. At 
first, sodium is retained, but after several days, normal sodium excretion 
is resumed despite continued administration of hormone. A normal secretion 
of the adrenal cortex is one requirement for the circulatory or renal read- 
justments which prevent undue accumulation of extracellular fluid. Although 
this homeostatic mechanism limits the increase in extracellular sodium, 
desoxycorticosterone induces continuous potassium loss in urine and, to a 
lesser extent, in feces so long as the diet contains ample sodium. Ammon- 
ium excretion in urine is increased without a fall in urine pH. If sodium 
intake is very low, these effects of mineralocorticoid excess on electrolyte 
balance are minimized or abolished. 

These initial signs of mineralocorticoid excess are soon followed by 
further evidences of potassium depletion. There is increasing thirst and 
large volumes of dilute urine appear. Renal concentrating power is im- 
paired, although urine flow can still be reduced by water deprivation or 
injection of vasopressin. Lassitude, muscular weakness, paralysis, and 
disturbances of cardiac action may follow, especially if sodium chloride is 
added to the diet. Plasma sodium and bicarbonate are increased while 
potassium and chloride concentrations are abnormally low. 

Arterial hypertension appears in some patients after administration 
of corticosteroids. Other forms of potassium deficiency are generally 
associated with a fall in blood pressure, sometimes with vascular collapse. 
Arterial pressure is more readily increased in animals with reduced func- 
tioning kidney substance. 

Medical News Letter, Vol. 32, No. 3 

An excess of Cortisol (hydrocortisone) induces a variable group of 
symptoms and signs often designated "Cushing's syndrome. " The appear- 
ance of hypertension, edema, polyuria, weakness, and hypokalemia with 
hypochloremic alkalosis demonstrates the mineralocorticoid effects of Cor- 
tisol which are usually accompanied by abnormal fat distribution, loss of 
muscle mass, weakness of connective tissue and blood vessels, altered 
organic metabolism, and other abnormalities. Most patients with adrenal 
cortical tumor show several signs of "Cushing's syndrome", but in certain 
instances, the hypertensive, renal, and electrolyte abnormalities are so 
prominent and the other signs so inapparent that the diagnosis of nephritis 
may be considered. 

When aldosterone was discovered to be the most potent mineralocor- 
ticoid secreted by the adrenal cortex, the output of this new hormone was 
estimated in patients with hyperadrenocorticism due to tumor or hyperplasia. 
Some of these patients showed excess aldosterone excretion. Other patients 
whose output of aldosterone was within normal limits showed predominant 
evidences of mineralocorticoid effect and, in rare instances, no recognized 
signs of "Cushing's syndrome" despite significantly increased excretion of 
17-hydroxycorticoids. Evidently, mineralocorticoid actions are not depen- 
dent solely on aldosterone, but may result from an excess of other adreno- 
cortical hormones. 

Adrenocortical carcinoma or bilateral hyperplasia commonly secretes 
an excess of several hormones which may appear as 17-ketosteroids, 17- 
ketogenic steroids, 17-hydroxycorticoids, and aldosterone in urine; and 
they may induce mixed biochemical and clinical patterns with elements of 
virilism, Cushing's syndrome, or mineralocorticoid excess. 

Differential diagnosis of mineralocorticoid excess from other forms 
of hyperadrenocorticism may be difficult because various mixtures of hor- 
mones produce mixed syndromes which defy simple classification. Here, 
concern is not only with clinical and laboratory findings and with patterns 
of hormone secretion, but also with the histopathology which can be deter- 
mined with certainty only by surgical exploration. There is also a curious 
mineralocorticoid-like syndrome associated with certain forms of carcinoma 
not arising in adrenal or pituitary glands. 

As yet, it is too early to state what the ultimate minimum require- 
ments for diagnosis will be. The minimum findings necessary for diagnosis 
in the past may be excessive when viewed in light of information available 
today. For the time being, the key finding will probably be arterial hyper- 
tension. This may be asymptomatic and may appear benign during the early 

Study of renal function may provide helpful information. Polyuria and 
polydipsia are important when present, but ordinary volumes of modestly 
concentrated urine may be excreted. Some limitation of concentrating power 
may be present and the normal action of pitressin in raising urine osmolarity 

Medical News Letter, Vol. 32, No. 3 

may fail even though there is some effect on urine flow. Neutral pH and 
low titratable acidity are regularly present, together with an unexpectedly 
high urine ammonia excretion in freshly voided urine. Bacteria growing in 
urine, or active pyelonephritis, could lead to an alkaline urine with high pH, 
low titratable acidity, and a high ammonia. Such a strongly alkaline urine 
would not be typical of mineralocorticoid excess in which the urine is more 
likely to be neutral. Urine cultures may be necessary to rule out an active 
urinary tract infection. Pyelonephritis and nephrosclerosis are possible 
late complications of mineralocorticoid excess. 

Other evidence of mineralocorticoid excess is usually found in the 
form of reduced sodium concentration and increased potassium to sodium 
ratio in sweat, saliva, and stool. 

If an adrenal tumor is visible in roentgenograms, including tomograms, 
pyelograms, or films taken after insufflation of oxygen in the presacral area, 
this information will facilitate surgery. The decision to operate should not 
rest on the roentgenologist because the tumor may be too small to demon- 
strate with certainty. Any patient who shows the definitive pattern of min- 
eralocorticoid excess should be explored. An adenoma may be very small 
and elusive even when the adrenals are exposed. Removal of a tumor respon- 
sible for excessive secretion will result in cure, provided that secondary 
structural changes have not taken place. Early case finding and differential 
diagnosis are essential for the best result. (Luetscher, J. A. Jr. , Editorial, 
The Syndrome of Mineralocorticoid Excess: Ann. Int. Med., 48: 1424-1431, 
June 1958) 

» 3& ife A sSc A 

Osmotic Diuretic Treatment of Refractory Edema 

Osmotic diuretics exert their action through physical rather than cel- 
lular metabolic effects. Osmotic diuretic action depends upon the presence 
of nonabsorbable particles within the isosmotic proximal tubule. These 
nonabsorbable particles cause retention of water within the proximal tubule 
to maintain a constant total osmolar concentration of 310 mOsM. per L. 
As compared with the preosmotic diuretic baseline, the water that is so 
retained progressively dilutes the sodium in the fluid as it traverses the 
proximal tubule Thus, an unchanged cell surface area containing the active 
metabolic sites for sodium resorption is exposed to a fluid of progressively 
lesser sodium concentration. The absorbing sites being less saturated, less 
sodium particles are absorbed (despite unaltered avidity of the individual 
cell sites), and more sodium particles are passed on distally. Within the 
proximal tubule, the additional nonabsorbed sodium and accompanying anions 
behave as osmotic diuretic particles and retain water that also is passed 
distally. In the distal convoluted tubule, absolute quantities absorbed, even 

Medical News Letter, Vol. 32, No. 3 

when maximal, are small fractions of the increased total quantities pre- 
sented and explain the inability of the distal tubule to greatly modify the 
nature of the fluid presented to it. Urine during such marked osmotic diur- 
esis is similar to the fluid leaving the proximal tubule in total concentration, 
pH, and individual ion concentrations. During such osmotic diuresis, the 
administration of a hypertonic solution (such as 1500 mOsM. per L. ) cou- 
pled with excretion of urine with a 300 to 350 mOsM. per L. concentration 
indicates a net loss of solute. 

Osmotic diuretics have been tried in refractory edema, both succes- 
ses and failures having been reported. However, the sparsity of data and 
the infrequency of their use suggest that they have not been generally effec- 
tive. From theoretical considerations, the limiting factor for their effec- 
tiveness is the presence of an adequate filtration rate to allow enough osmotic 
diuretic particles to reach the tubular lumen. Mercurial and osmotic diure- 
tics potentiate each other's effects. 

Mannitol, regarded as an almost inert nontoxic hexose, excreted by 
glomerular filtration alone, is an osmotic diuretic available for parenteral 
injection. The experience with mannitol administered intravenously with 
and without a mercurial diuretic in the treatment of refractory edema is the 
basis of this report. 

Subjects were chosen who had marked edema of nephrosis, cardiac 
failure, or cirrhosis that was refractory to dietary salt restriction (less 
than 500 mg. of sodium per day) plus the usual diuretics, singly and in 
combination. In all patients, use of mercurial diuretics, aminophylline, 
ammonium chloride, and Diamox was unsuccessful. 

Because of prolonged refractory edema, diuresis with mannitol admin- 
istered intravenously was attempted. The dietary sodium content was con- 
stant for several weeks before, during, and after mannitol administration 
in all cases. Water intake was ad libitum. Patients were treated with 
infusions of 25% mannitol intravenously in amounts up to 2000 ml. (500 gm. ) 
over periods of 4 to 8 hours. Usually a priming dose was followed by a 
slower infusion. Interruptions of the infusions occurred occasionally. A 
mercurial diuretic (Thiomerin) was given intravenously as single 2 -ml. 
doses, or as 2 1-rnl. doses 3 to 5 hours apart. These data demonstrate 
the effectiveness of an osmotic diuretic combined with a mercurial diuretic 
in treatment of refractory edema. 

The increased effectiveness of the combination of an osmotic and a 
mercurial diruetic probably can be explained by their known different actions, 
Mannitol, by its water-retaining and sodium -diluting action, decreases the 
numbers of sodium -absorbing sites of the tubular cells that are exposed to 
sodium; Thiomerin reduces the avidity of each of these decreased numbers 
of sites for sodium resorption. The combined effects result in great prox- 
imal tubular rejection of sodium (and accompanying anions). Both mannitol 
and nonabsorbed sodium (due to mercurial effects on tubular cells) have 

10 Medical News Letter, Vol. 32, No. 3 

been shown to act as osmotic diuretics. The nonabsorbed ions and the man- 
nitol retain water i so sm otic ally in the proximal tubule and thus present 
excessive amounts of water and electrolytes to the distal tubule which are 
followed by excess excretion. It would be expected that any osmotic diuretic 
could be effectively combined with any metabolic diuretic that acted directly 
on the active cell mechanism for sodium transport. The factors influencing 
excretion of sodium are so numerous and variable that no absolute values 
of sodium excretion may be expected for given doses of mercurials, osmotic 
diuretics, or combinations of diuretics. \Afhat is demonstrated is the ability 
of osmotic diuretics to increase the tubular rejection of sodium from what- 
ever level of rejection existed immediately prior to their use. 

Despite the great losses of water, sodium, and chloride during the 
course of combined mannitol-Thiomerin treatment, no clinically significant 
changes of serum sodium, potassium, chloride, or bicarbonate concentra- 
tions occurred. 

No substantial difference was found between the natriuretic or diuretic 
effects of mannitol plus Thiomerin in the patients with refractory edema of 
renal, cardiac, or hepatic origin. The diuretics were effective in shifting 
toward greater tubular rejection of sodium and water. The similarity of 
diuretic effects conforms with the concept that in these different states 
excessive sodium resorption by tubular cells due mainly to increased aldos- 
terone effect is the final common pathway for the development of edema. 

The clinical value of osmotic diuretics in refractory edema must be 
evaluated by more extended studies. The hazards of pulmonary edema in 
cardiac patients may be minimized by use of adequate doses of urea or other 
osmotic diuretics that are distributed throughout body water rather than 
extracellular fluid alone. In cirrhotic patients, the effects of repeated treat- 
ment gradually to remove extensive ascites and peripheral edema must be 

The use of (physical) osmotic diuretics in large adequate doses in com- 
bination with (metabolic) tubular cell sodium resorption blocking diuretics 
should be considered when edema states are refractory to all other diuretic 
therapy. (Bernstein, L. M. , Blumberg, B. , Arkin, M. C. , Osmotic Diuretic 
Treatment of Refractory Edema: Circulation, XVII ; 1013-1019, June 1958) 

* # $ * aje * 

Change of Address 

Please forward requests for change of address for the News Letter to: 
Commanding Officer, U. S. Naval Medical School, National Naval Medical 
Center, Bethesda 14, Md. , giving full name, rank, corps, and old and new 



Medical News Letter, Vol. 32, No. 3 11 

Myelo scintigraphy 

The use of radioactive iodinated human serum albumin (RIHSA) in 
localizing lesions of the spinal canal has been described by Bauer and Yuhl 
in a preliminary report. Since June 1955, the authors have employed this 
technique for localization of lesions which show clinical evidence of spinal 
cord or root compression and varying degrees of spinal block. 

The technique used is similar to that outlined by Bauer and Yuhl. If, 
at the time of the usual diagnostic lumbar spinal puncture there is evidence 
of a partial or complete spinal block, the isotope laboratory is called and 
approximately 300*/<s of RIHSA in 5 cc. of normal sterile saline is injected 
before the spinal needle is withdrawn. If possible, the patient is placed in 
the knee-chest position for at least 15 minutes. If not, the foot of the bed 
is elevated. One hour after injection, the patient is scanned, using a com- 
mercially available, mechanical apparatus. The authors believe that this 
equipment is already somewhat outmoded. 

The scintigrams obtained are referred to as myeloscintigrams. The 
myeloscintigram is orientated as to level by means of a lead marker placed 
on the patient's back, its location being identified on the scintigram. A 
roentgenogram of the involved area is made with the lead marker still in 
position. The scintigram is then superimposed upon the roentgenogram for 
localization of the spinal block. The authors noticed no significant untoward 
reaction in 28 patients subjected to this procedure. 

Early cases in this series did not all have clinical evidence of a spinal 
block, but they are included for the sake of completeness. At the present 
time, the technique is usually reserved for those individuals with clinical 
evidence of either partial or complete spinal block. 

Of the 28 patients studied thus far, 12 myeloscintigrams were reported 
as showing positive evidence of an abnormality, such as complete block, 
partial block, or interference with the circulation of the spinal fluid. Ten 
such reports were verified by operation. One was reported as showing a 
filling defect at the fourth lumbar inter- space, but laminectomy showed a 
herniated intervertebral disk at the fifth lumbar intervetebral space. The 
twelfth positive case was clinically diagnosed arachnoiditis and not operated 

Of 9 cases reported as negative, 2 were, found to have small herniated 
disks at operation. One had diffuse arachnoiditis and the remaining 6 were 
not operated upon. 

Seven myeloscintigrams were reported as uncertain. Six of these 
were considered to be suggestive of a spinal lesion. Three of the latter were 
operated upon and shown to have a lesion at operation. In the remaining 4, 
clinical evidence was not considered sufficient to warrant operation. 

It is of special interest to note that in the 9 proved cases with evidence 
of partial or complete block at the time of spinal tap, the myeloscintigram 

12 Medical News Letter, Vol. 32, No. 3 

localization was correct in all, or 100%, of cases. In these cases, the 
authors believe their myeloscintigraphy to be of greatest value. 

That myeloscintigraphy may ultimately prove to be of value in help- 
ing to establish the diagnosis of inflammatory as well as space occupying 
lesions of the spinal cord and canal is the belief of the authors. Further 
investigation of this possibility is at least indicated. 

The simplicity of the technique makes it highly desirable and in this 
manner somewhat comparable to air myelography. Camp, in an excellent 
article on contrast myelography, has enumerated the advantages and dis- 
advantages of air myelography; it appears to the authors — in their hands, 
at least — that myeloscintigrapny has fewer side reactions and will prove 
to be more satisfactory for the demonstration of partially obstructing les- 

The average time required for scanning has been 25 minutes when 
300uC were used. Because the RIHSA is rather rapidly eliminated from 
the spinal fluid and excreted, there is no necessity to, or difficulty in, re- 
moving it as there is with potentially irritating radiopaque materials. The 
patient is much more comfortable during this procedure than during oil 
contrast myelography and there is no need for fluoroscopy. (Ferryman, 
C. R. , Noble, P. R. , Bragdon, F. H. , Myeloscintigraphy: A Useful Pro- 
cedure for Localization of Spinal Block Lesions: Am. J. Roentgenol., 
80: 104-111, July 1958) 

Cardiac Rehabilitation 

Increasing interest in "cardiac rehabilitation" not only by physicians, 
but by public, governmental, and voluntary agencies has demanded that the 
medical profession give a satisfactory definition of this term. Direction is 
also needed for future energies to be expended in cardiac rehabilitation by 
those interested in this problem. 

As part of a national survey of cardiac rehabilitation sponsored by 
the National Heart Institute, a questionnaire was sent to a number of the 
nation's leading cardiologists and internists who have had broad experience 
in cardiology, asking their definition of the term, their opinions as to how 
rehabilitation of the patient with cardiac disease is most effectively accom- 
plished, and what future course should be taken in assuring the cardiac 
patient of his place as an effective member of society. The opinions of 36 
of these physicians are contained in this article. It should be emphasized 
that these are doctors with consulting practices who daily face the problems 
of the patient with a diseased heart. The questions posed were: 

1. What would you consider a proper definition of rehabilitation, 
especially as applied to persons with cardiovascular disease? 

Medical News Letter, Vol. 32, No. 3 13 

2. What do you believe are the major problems faced by the prac- 
ticing physician in his efforts to rehabilitate individuals with cardiovas- 
cular disease ? 

3. What do you think should be done to solve some of these problems? 

4. In the order of their importance, what measures have you found 
of value in the rehabilitation of your cardiac patients? 

5. Please comment on your practical experience in the rehabilitation 
of patients with the following cardiovascular diseases: (a) congenital 
heart disease, (b) rheumatic heart disease, (c) hypertensive cardiovas- 
cular disease, (d) coronary artery disease, (e) cerebral vascular dis- 
ease, (f) neurocirculatory asthenia, (g) iatrogenic heart disease, (h) 
syphilitic heart disease, (i) subacute bacterial endocarditis. 

6. Give five or six examples of rehabilitation from your own practice. 
A review of answers to the questions indicates that there is a fairly 

clear idea — in the minds of physicians at least — as to the meaning of car- 
diovascular rehabilitation. Also, it is evident that these practicing phys- 
icians believe that the most important factors in cardiovascular rehabilitation 
are: (1) proper medical treatment of the patient so far as disease processes 
are concerned; (2) the proper attitude of doctor and patient about the disease 
itself with emphasis on the possibility or probability of a return to a useful 
life and the elimination of fear concerning heart disease; (3) the need of 
correcting certain difficult customs and laws with respect to disability, 
compensation, and decision of unemployability by various industries; and 
(4) in apparently rare cases, the utilization of work classification units and 
their facilities for vocational counseling. 

Rehabilitation has been proved possible in the majority of cardiovas- 
cular conditions, including congenital heart disease, rheumatic heart disease, 
hypertensive cardiovascular disease, coronary heart disease, and subacute 
bacterial endocarditis. There are two conditions in which this is still rela- 
tively difficult: cerebral vascular disease and neurocirculatory asthenia. 
However, emphasis should be put on the favorable longevity of individuals 
with neurocirculatory asthenia and the fact that they often "outgrow" some 
of their difficulty as they adjust themselves to their problems. All the phys- 
icians queried have had interesting experiences in the rehabilitation of their 
cardiac patients, the rehabilitation coming sometimes through the physician, 
but at other times, through the ability of the patient himself to adjust to his 
difficulties. (Williams B. , White P. D. , Lee, P. R. , Rusk, H. A. , Cardiac 
Rehabilitation - A Survey of Cardiologists* Opinions: Am. Heart J., 56: 
107-111, July 1958) 

>k & A A ;k j"x 

Use of funds for printing this publication has been approved by the 
Director of the Bureau of the Budget 19 June 1958. 

14 Medical News Letter, Vol. 32, No. 3 

Iron as a Therapeutic Agent in Pediatric Practice 

This article discusses therapeutic uses of iron in light of current 
knowledge of iron metabolism and the author's experience in dealing with 
hematologic problems in pediatric patients. 

Theoretically, iron should be administered only to prevent the devel- 
opment of iron deficiency. If early recognition of the several factors res- 
ponsible for the development of iron deficiency was possible in each patient, 
preventive administration of iron would eliminate the deficiency states so 
commonly encountered in present day pediatric clinics. The conditions in 
which a physician might anticipate the eventual development of frank iron 
deficiency are listed in a table. In these situations, iron therapy is indi- 
cated for the prevention of clinical iron deficiency. If preventive adminis- 
tration of iron is not used, iron deficiency requiring appropriate treatment 
of the primary cause and administration of iron will be necessary. 

That normal infants are born with sufficient iron to satisfy their needs 
for the first few months of life is generally accepted. The largest part of 
this iron reservoir is to be found at the time of birth in the circulating hemo- 
globin mass itself. The hematocrit — and particularly the red cell mass — 
per unit of body weight is significantly greater at birth than in older infants. 
As the fetal erythrocytes disappear from the circulation, iron is retained 
in the body and satisfies the larger part of the demands for iron of future 
growth. It is evident that any loss of infant blood prior to, during, or shortly 
after birth will deprive the growing infant of sources of iron that cannot be 
replaced from normal dietary sources. 

Considerable controversy exists as to the significance of iron defic- 
iency in the mother during pregnancy in the causation of iron deficiency in 
early infancy. In an American urban population, Lund and co-workers 
recently demonstrated a high incidence of iron deficiency during late preg- 
nancy. How severe such a deficiency may be before the supply of iron to 
the infant is compromised remains an unanswered question. In the pres- 
ence of a clinically apparent iron deficiency in the mother, administration 
of iron supplementation to the infant for 2 or 3 months early in life is recom- 

The Physicians' Desk Reference lists 170 preparations recommended 
as useful in the prevention and treatment of iron deficiency anemias. None 
is more effective than simple ferrous sulfate, most are more expensive, 
and many are more dangerous. 

Either ferrous sulfate or ferrous gluconate is a suitable therapeutic 
agent. Ferrous sulfate is available in palatable concentrated form which 
can be administered in drop doses with symptoms of gastrointestinal intol- 
erance encountered rarely in infants and young children. 

The recommended therapeutic practice is to use simple ferrous salts 
in the prevention and treatment of iron deficiency states, A total dose of 

Medical News Letter, Vol. 32, No. 3 15 

60 to 75 rog. of elemental iron is given daily. The medication is given in 
at least two divided amounts each day to assure optimum absorption. The 
practice of giving gradually increasing doses of iron and administering the 
medication after meals is commonly advocated in adults where gastrointes- 
tinal intolerance to iron salts is not uncommon. With the ferrous sulfate 
concentrates available, gastrointestinal symptoms in infants or young chil- 
dren have not been commonly encountered even when starting therapy with 
full therapeutic doses and giving the medication to fasting subjects. 

Less concentrated forms of iron in liquid form, such as elixirs of 
ferrous sulfate, have been found effective medications for use in infants 
and young children in the past. Staining of the teeth and the required 4 to 
8 cc. doses which may be difficult to administer frequently to very young 
infants are distinct disadvantages to their use when compared to currently 
available iron concentrates. iVhere cost is a major factor in treatment, 
elixirs of ferrous sulfate will be found somewhat less expansive than the 
concentrated preparations. 

In older children, tablets of ferrous sulfate (0. 2 gm. ) or ferrous glu- 
conate (0. 3 gm. ) will often be more suitable than liquid preparations. One 
or two tablets are given 3 times daily providing a total daily dose of 220 
to 440 mg. of iron. In older children, gastrointestinal symptoms of nausea, 
vomiting, or abdominal pain will occasionally be encountered if iron is taken 
when the stomach is empty. In addition, school-aged children will take the 
medication with more regularity if it is given at mealtime. For these rea- 
sons, iron tablets are best taken 3 times daily with, or immediately follow- 
ing, meals. 

It is regrettable that all too often parents and physicians alike have 
a poorly controlled enthusiasm for injectable forms of medication. It is 
hoped that the enthusiasms for x-ecently available injectable preparations 
of iron would be seriously tempered by the following well established 
facts regarding iron compounds now available for both intravenous and 
intramuscular injection. 

Only a rare patient with iron deficiency anemia fails to tolerate and 
respond satisfactorily to iron salts given by mouth. 

Toxic reactions following parenterally administered iron do occur 
and may occasionally be severe. 

The body has no normal mechanism for the excretion of iron. Indis- 
criminate use of parenterally administered iron for long periods of 
use in patients not iron deficient may produce toxic iron-overload. 

There is no increase in the rate of hemoglobin production in patients 
treated with parenteral iron when compared to those treated with oral 
iron that is clinically significant. 

The response to iron therapy is highly predictable and will be mani- 
fest in an improvement in general well-being with rather prompt disappear- 
ance of symptoms of irritability and anorexia. Laboratory studies will show 

16 Medical News Letter, Vol, 32, No. 3 

a reticulocyte sis in proportion to the severity of anemia present; a grad- 
ual predictable increase in hemoglobin concentration will result. The 
erythrocyte count will also increase. 

Specific diagnosis is the keystone to successful and safe iron therapy. 
Chronic toxic iron overload is a potential danger in any patient being given 
iron in the absence of a proper diagnosis. (Smith, N. J. , Iron as a Thera- 
peutic Agent in Pediatric Practice: J. Pediat. , 53: 38-50, July 1958) 

jf: sje sj; %. ifc # 

Sarcoma of the Mammary Gland 

Primary sarcoma of the mammary gland has long been recognized as 
an infrequently occurring, but distinct, entity. The present study of the 
clinical and microscopic features of sarcoma of the breast was undertaken 
in an attempt to bring some clarifications to such factors as the history and 
physical findings, gross and microscopic pathologic observations, clinical 
course, and appropriate therapy associated with this type of primary neo- 
plasm of the breast. 

The records of all patients seen at the Ma yet Clinic during the 50 years 
between 1907 and 1956 inclusive, whose diagnoses contained the term sar- 
coma in reference to a tumor of the breast, were selected for study. The 
histories and operative and pathologic reports were reviewed and abstracted. 
The gross and microscopic pathologic features of the available operative 
specimens were studied and evaluated. The presence of a benign epithelial 
component in a neoplasm, the stroma of which was richly cellular, indicated 
that the fundamental lesion was a fibroadenoma. Because the clinical course 
of fibroadenomas is benign, these lesions have been excluded from this study. 

In 34 cases, there were microscopic features of the primary lesion 
which were consistent with a diagnosis of true primary sarcoma of the breast. 
The mean age of the 34 patients was 49. 2 years, the extremes being 21 and 
69 years. There were 33 women and 1 man in the series. The incidence 
according to side of the body was equal, 17 instances of the lesion having 
been noted on each side. The mean duration of the lesion as recorded in 
28 cases was 55. 05 months. A period of rapid growth averaging 4. 25 months 
was noted in 18 cases. Antecedent trauma was a complaint in only 1 instance. 
Loss of weight just prior to the initial examination was noted in 6 patients, 
only 1 of whom had evidence of metastatic disease at the time of the com- 
plaint. Pain in the involved breast occurred in 14 of the 34 cases, but the 
detailed character of the pain was not recorded. 

Retraction of the nipple occurred in 2 instances, in 1 of which this 
complication was bilateral. Fixation of the skin overlying the tumor mass 
was recorded in 10 instances. Change in color of the overlying skin had 
occurred in 7 cases. Ulceration of the overlying skin occurred in 3 patients. 

Medical News Letter, Vol. 32, No. 3 17 

Palpable ipsilateral involvement of the axillary lymphatic vessels were 
demonstrated in 10 of the 34 cases. 

In general, the gross lesions were circumscribed, partially or wholly 
encapsulated, and irregular or lobed on the exterior surfaces. The size of 
the lesions varied, the extremes being 1. 5 and 15 centimeters in diameter. 
The tumors generally were firm. The cut surface bulged, was smooth and 
glistening, either homogenous or whorled in appearance, and contained 
occasional areas of necrosis. Fixation in formalin had altered the natural 
colors of the tumors which were, therefore, not recorded. 

Six groups of primary sarcomas of the breast were found in the 34 
cases in this series. These groups were based on cell type and were clas- 
sified as follows: fibrosarcoma, 14 cases; rhabdomyosarcoma, 4 cases; 
osteogenic sarcoma, 5 cases; liposarcoma, 1 case; malignant mixed tumor 
of breast, 5 cases; and mixed fibrosarcoma and carcinoma, 5 cases. 

A period of latency or long duration prior to a period of rapid growth 
are two characteristics frequently associated with sarcoma of the breast. 
The duration of either or both of these characteristics obviously varies 
according to many factors. 

Pain in the involved breast in more than one -third of the cases con- 
firmed the impression of others that such a complaint deserves more than 
passing consideration by the clinician. 

Fixation of the overlying skin in itself was found to be of little sig- 
nificance. The nature of the fixation was of some concern; in the majority 
of cases, it was described as being stretched or lacking mobility because 
of pressure and tension. The edema, orange-peel appearance, and retrac- 
tion of the skin so frequently associated with carcinoma of the breast were 
lacking. Although actual involvement of the integument by the tumor process 
was not demonstrated in any of the cases in this series, it was reported by 

The association of palpable involvement of axillary lymphatic vessels 
by primary sarcoma of the breast is of little significance because these 
tumors rarely, if ever, metastasize to regional lymph nodes. Smithy 
reported 32 cases in. which mixed malignant processes of the breast were 
found to contain carcinoma as well as sarcoma. In Smithy's series, com- 
piled from the literature, 11 instances were found in which axillary nodal 
metastasis by the carcinomatous element had been demonstrated. This 
observation obviously becomes significant in determining a course of sur- 
gical therapy in mixed lesions containing carcinoma. 

The authors conclude that true primary sarcoma of the breast is a 
distinct clinical and pathologic entity, and that this lesion may contain 
one or more types of malignant mesenchymal tissue intimately admixed 
with malignant epithelial tissue. They further conclude that associated 
palpable involvement of axillary lymphatic vessels is of little significance in 
determining the appropriate surgical therapy or ultimate clinical course 

18 Medical News Letter, Vol, 32, No. 3 

associated with sarcoma of the breast. They are of the opinion that true 
primary sarcoma of the breast rarely, if ever, metastasizes to regional 
lymph nodes. 

The authors suggest that primary sarcoma of the breast, although 
occasionally associated with ulceration, rarely invades the overlying integ- 
ument, but that it is capable of metastasizing and often does metastasize, 
primarily by way of the blood stream, most frequently to the lungs. They 
believe that simple mastectomy with excision of the underlying pectoral mus- 
culature is adequate therapy for sarcoma of the breast not containing a malig- 
nant epithelial component, and that primary sarcoma of the breast which also 
contains demonstrable carcinoma in fresh-frozen sections should be treated 
by radical mastectomy. They are convinced that wide local excision — when 
feasible — is indicated in the treatment of recurrent sarcoma of the breast. 
(Botham, R. J. , McDonald, J. R. , Clagett, O. T. , Sarcoma of the Mammary 
Gland: Surg. Gynec. & Obst. , 107 : 55-61, July 1958) 

;Js j{c + $ Up If 

Promethazine as an Adjunct to Obstetrical 
Analgesia and Sedation 

The majority of obstetricians feel that analgesia and sedation are in- 
dicated during labor, but that routine measures for relief of the patient's 
pain are generally inadequate and dangerous to the infant. 

Read's writings have revived interest in the psychological aspects of 
pregnancy and parturition, about which even yet very little is known. His 
method involves a system of prenatal indoctrination and a regimen of mus- 
cular exercises designed to allay the apprehension of the patient and to aid 
her in achieving voluntary physical relaxation during labor. 

In this study, the authors have incorporated some of Read's prenatal 
indoctrination and have employed a different method of obtaining analgesia 
and sedation during labor. They have attempted to decrease the dosage of 
respiratory depressant drugs used and, at the same time, obtain what is 
considered safe and adequate analgesia and sedation with no detrimental 
effect upon the patient or infant. 

Simple psychotherapy should be practiced as part of the prenatal prog- 
ram from the earliest visit to the physician. During pregnancy, the authors' 
patients make 12 to 14 visits to their office — more, if advisable. At each 
visit, after the routine examination has been completed, the patient returns 
from the examining room to the private office for a talk with her obstetri- 
cian. This verbal contact with the patient does more to establish rapport 
and dismiss the fearful unknowns of pregnancy than sending her home armed 
with printed literature only. Every effort is made to nurture in the patient 
a will to conscious participation in the birth process. The risk to the infant 

Medical News Letter, Vol. 32, No. 3 19 

of respiratory embarrassment from narcotics is stressed, as well as the 
fact that by insisting on delivery in the unconscious state, she is depriving 
herself of a profound experience to which she has a natural right. She is 
assured, however, that medication will be provided to relieve the most 
painful and exhausting phases, although a certain amount of discomfort 
cannot safely be avoided. 

In the authors' practice, the results obtained with meperidine and 
scopolamine in the dosages usually employed have coincided with the exper- 
iences of many others. Especially in the conduct of prolonged or severe 
labor or in association with a general anesthetic for delivery, the well 
known depressant effects have been a handicap. 

Previously, the authors used oral promethazine (an ethyl phenothia- 
zine hydrochloride, which differs from chlorpromazine in having a branched 
side chain and in lacking the chlorine atom on the phenothiazine ring) for 
control of nausea and vomiting in pregnancy. A soporific effect was a fre- 
quent observation. Attention, therefore, was turned to parenteral use of 
promethazine in the hope of developing a more satisfactory regimen for 
management of labor. 

The present investigation was begun in May 1955 and is continuing. 
Up to the time of this report (January 1957), the series totaled 500 private 
patients ranging in age from 16 to 42 years, with an average of 27 years. 
About 50% were primiparas. Gravidity ranged from i to xiii, and parity 
from to xi. 

All of these patients — even the most stable — exhibited some degree 
of nervousness and apprehension on admission despite the careful prenatal 
instruction they had received. The younger primiparas particularly were 
disturbed by the discomforts attending the first stage. At the onset of each 
contraction, such patients without medication usually became tense and fear- 
ful in anticipation of the full impact of the pain regardless of reassurances 
and instructions to "relax. " 

In 75% of all patients at term, delivery was spontaneous; low forceps 
were used in 14%. Breech extractions were performed in 4%; and in 3%, 
rotation with Kielland forceps was necessary. Mid-forceps with manual 
rotation were used in 0. 6%; and cesarean section was required after failure 
of trial labor in 0. 4%. Seven pairs of twins and 9 single infants were deliv- 
ered by breech extraction. 

In 15 to 30 minutes after the first injection, a definite general relax- 
ation was noticeable regardless of the size of the dose. On administration 
of subsequent doses, the onset of analgesia and sedation was even more 
rapid and the duration usually longer. Some patients dozed and others fell 
into a light sleep from which at times they awakened temporarily as con- 
tractions became more forceful. They could be aroused easily, answered 
questions intelligently, and cooperated in response to directions. 

The great majority (88%) of the patients received adequate sedation 
with one dose consisting of 100 mg. promethazine, 50 mg. meperidine, 

20 Medical News Letter, Vol. 32, No. 3 

and 1/150 or 1/100 grain scopolamine, administered on dilatation of the 
cervix to 2 to 4 cm, A second dose, usually of 50 mg. of promethazine and 
50 mg. of meperidine, but without scopolamine in some cases, was required 
by 10% in 3 to 5 hours after the first dose. Two percent of the patients re- 
quired a third dose, averaging 50 mg. promethazine, 50 mg. of meperidine, 
and 1/200 grain of scopolamine about 6 hours after the second. Adequate 
analgesia and sedation were also provided by similar doses administered 
during a trial of labor which preceded one cesarean section in the series. 
The authors now routinely use promethazine 100 mg. , meperidine, 50 mg. , 
and scopolamine 1/150 grain, administered 2 hours before operation in all 
cases of elective cesarean section with excellent results. 

The authors found analgesia and sedation predictable with this method 
and believe the measures described will stimulate an important change in 
the management of labor. The obstetrician will be obliged to devote a little 
more time to each patient during pregnancy, persuading her that delivery 
can be accomplished without narcosis, yet without excessive pain, and that 
the physical benefits to the infant are incalculable. 

The influence of the premedication on the duration of labor appears 
especially noteworthy because it has been generally considered that normal 
labor averages about 17 hours in length. 

Promethazine was administered to 500 private patients in an attempt 
to provide more adequate sedation in labor, yet avoid respiratory embarrass- 
ment in the infant. Premedication was first administered on dilatation of the 
cervix to 2 to 3 cm. In most cases, adequate sedation was obtained with one 
dose of 100 mg. promethazine, administered intramuscularly, with 50 mg. 
meperidine and 1/150 or 1/100 grain scopolamine injected in a separate 

Labor in uncomplicated cases was definitely shortened. In 87% of the 
primiparas, labor was without complication; in 96% of these, delivery occurred 
in 1-1/2 to 7 hours after the first injection and 50% were delivered in a total 
of 3 to less than 8 hours. There was no respiratory depression in the infants 
as a result of the medication and, after a 2-year follow-up by their pediatri- 
cian, no delayed or unrecognized effect has been noted. (Gordon, L. E. , Ruffin, 
C. L.. , Promethazine as an Adjunct to Obstetrical Analgesia and Sedation - 
A Series of 500 Cases: Am. J.Obst. fcGynec. , 76:147-151, July 1958) 

$ $ ijc $ $ sje 

Occupational Medicine Program - Scientific Assembly 
of American Medical Association 

The Scientific Assembly of the American Medical Association convened 
in San Francisco, Calif. , June 23-27, 1958. The Section on Preventive Med- 
icine met on three successive afternoons. Occupational medicine was well 

Medical News Letter, Vol. 32, No. 3 21 

represented by such outstanding men as Robert A. Kehoe, Frank Princi, 
Rutherford T. Johnstone, Edward P. Luongo, and Edward J. Tracy — all 
holding offices in the Section. 

The Program of the Scientific Assembly contained the following ab- 
stracts of papers presented at the joint meeting of the Section on Preven- 
tive Medicine and the American Academy of Occupational Medicine: 

The Occupational Diseases: Diagnosis and Proper Method of Reporting 

Statistics derived from the reporting of communicable diseases ap- 
proach a high degree of accuracy. The information obtained serves to 
prevent or control such diseases. The primary objective of occupational 
medicine is likewise prevention. In most states, the law requires the 
reporting of an occupational disease, but unlike Public Health statistics, 
those obtained by state agencies about the incidence or cause of an occu- 
pational disease are almost completely worthless. Both the medical pro- 
fession and the administrators of Workmen's Compensation are at fault. 
Because the law requires immediate reporting after the first examination 
upon a standard form of insufficient space, the physician is encouraged 
and yields to the conjectural type of diagnosis. State agencies and the 
Association of Industrial Accident Commissions should change the re- 
quirements to the narrative form of reporting. (Rutherford T. Johnstone) 

The Physician as Advisor to Industrial Management 

Industry provides a broad spectrum of opportunity for economic ad- 
vancement to physicians generally. At the lower end is the simple 
arrangement requiring no unusual medical talent whereby a fee is de- 
rived from rendering an occasional technical service to an employee. 
In the middle range are the considerable benefits which the experienced 
industrial physician can derive from a career in occupational medicine 
devoted to the projection of a trained viewpoint. At the top of the spec- 
trum are the rewards to the rarely available physician having a com- 
bination of imaginative, analytical, and administrative talents shaped 
by medical perspective and who becomes an integral member of top 
industrial management. Assuming basic professional competence and 
an inquisitive attitude, the physician who advances in industry does so 
in proportion to his skill in speaking to, with, and for management in 
medical concepts adapted to the occupational environment. 

(Clifford H. Keene) 

The Problem Back 

The effect of significant actual trauma on spinal structures is not 
difficult to diagnose or to treat. Spinal tissues stretched, or disrupted, 
except nerve elements, heal by primary intention in a predictable length 
of time. The course of tissue healing is toward rapid repair and 

22 Medical News Letter, Vol. 32, No. 3 

improvement, not toward chronicity. The so-called "Problem Back" 
occurs only when the element of chronicity arises. The exaggerated 
symptoms and prolonged disability of the individual so affected makes an 
initial diagnosis of acute back sprain suspect. Chronic back complaints 
are most commonly due to either disease, structural abnormality, en- 
vironmental conflicts, emotional attitudes, or a combination of one or 
more of these. In California, one-fifth of all cases of lost time are due 
to back injury and it is the most common single cause. 

{John E. Kirkpatrick) 

Hospital Employees: Corridor Consultations or Health Maintenence? 

Only recently considered as industrial plants, hospitals have, in some 
instances, developed employee health programs. Whereas such preventive 
medical efforts progress without too much difficulty in manufacturing sit- 
uations, the health service director in a hospital faces the competing 
practice of corridor medicine, and the frustrating poor documentation of 
the findings and recommendations resulting from this curbside consulta- 
tion. An opportunity exists for the general practitioner to exercise pre- 
ventive medical measures in the hospital setting, be it a small community 
installation or a large University Medical Center. As hospital employees 
usually are underpaid and have come from underdeveloped medical back- 
grounds, a strong positive program is needed, and the activity can be 
rewarding and satisfying. (Jean Spencer Felton) 

(OccMedDispDiv, BuMed ) 

Expired Air Resuscitation 

Extensive physiological measurements in 29 adult anesthetized patients 
demonstrated expired air resuscitation to be an efficient versatile method of 
artificial respiration. Reoxygenation of the patient's lungs is possible with 
four inflations, and within a circulation time, arterial oxygen saturation can 
be restored to normal. Carbon dioxide levels are concomitantly reduced. 
The data reported refute the widespread prejudice that a rescuer's exhaled 
air contains too little oxygen and too much carbon dioxide. By mild hyper- 
ventilation, the rescuer readily converts his exhaled air to a suitable resus- 
citating gas. He can perform the method for prolonged periods without undue 
fatigue or hypocapneic symptoms. 

Experience with mouth -to -mouth techniques and its variants in emer- 
gency resuscitation of hospital patients and physiological measurements 
made under controlled conditions indicate that two important precepts must 
be followed: (1) A patent airway must be promptly established and main- 
tained. (2) Inflation volumes of a liter or more must be delivered to the 

Medical News Letter, Vol. 32, No. 3 23 

adult victim's lungs at a rate of 12 to 20 per minute. (Elam, J. O. , Greene, 
D. G. , Brown, E. S. , Clements, J. A. , Oxygen and Carbon Dioxide Ex- 
change and Energy Cost of Expired Air Resuscitation: J. A. M. A. , 167 : 
328-334, May 17, 1958) (OccMedDispDiv, BuMed) 

A ric At A 'sic sic 

Seminar in Aviation Medicine 

The Third Annual Reserve Research Seminar in Aviation Medicine 
was held at the U. S. Naval School of Aviation Medicine in Pensacola, Fla. , 
May 12-25, 1958. Thirty-three Reservists of the Army, Navy, and Air 
Force attended. 

Among the attendees there were physicians, psychologists, basic 
medical scientists, engineers, and representatives of the professions of 
psychiatry, ophthalmology, dentistry, optometry, radiology, pathology, 
and electronics. 

The purpose of these Seminars is to provide Reservists with a broad 
understanding of the personnel and operational problems of Naval Aviation, 
and its role in the conduct of modern warfare. 

At the beginning of the Seminar, the Chief of Naval Air Training 
and his staff presented the logistics and training problems involved in the 
procurement, selection, training, and retention of Naval aviators capable 
of handling the complex expensive and "hot" aircraft now being delivered to 
the Fleet. 

The physics of the upper atmosphere, outer space, and of satellite 
launching were presented. These were followed by discussions of the bio- 
logical, physiological, and psychological problems which confront man in 
high speed, high altitude flight under all-weather and combat conditions. 
In addition, special presentations were made on the biological and psychol- 
ogical problems involved in the explorations of outer space. 

Visits and informal discussions were held with small groups in the 
various research laboratories. These included physiology, biochemistry, 
low pressure, acoustics, radiation, electron microscopy, ophthalmology, 
and psychology. 

The use of pressure suits to protect the pilot against gravitational 
forces in high speed maneuvers as well as in escape from aircraft at high 
altitudes was demonstrated. At the USAF Air Proving Ground Command, 
tests of planes and ordnance under climatic conditions simulating the tropics 
and arctic regions of the earth were observed. Small groups were led through 
a test hangar where six planes were undergoing tests at 65°F below zero. The 
change from 86°F outdoor temperature to this arctic cold in less than a min- 
ute was impressive. 

Captain C. F. Gell MC USN of the Aeronautical Medical Equip- 
ment Laboratory, Philadelphia, Pa. , described and showed movies of the 

24 Medical News Letter, Vol. 32, No. 3 

confinement of six volunteers for 7 days in a small cabin simulating con- 
ditions of space flight. Around-the-clock tests and measures were made of 
physiological conditions of the men and performance on psychological tests 
and problems of learning. 

Commander G. VV. Hoover USN discussed the ONR development prog- 
ram for a new electronic cockpit instrumentation and control system. This 
system provides the pilot with information permitting him to maneuver the 
aircraft under all weather conditions as if he were flying by visual contact 
on a clear sunny day. Radical new designs and miniaturization of compon- 
ents are major factors in making this design practicable. 

The seminar was planned and conducted by Commander H. A. Imus 
MSC USNR, a member of Naval Reserve Research Company 5-10, Naval 
Medical Research Institute, Bethesda, Md. The Office of Naval Research, 
in conjunction with the Naval Air Training Command and the Naval School 
of Aviation Medicine sponsored the Seminar with the approval of the Bureau 
of Naval Personnel, the Bureau of Medicine and Surgery, and the Bureau of 
Aeronautics. (ONR) 

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Environmental Sanitation Course 

Applications are invited from Medical Service Warrant officers inter- 
ested in assignment to duty under instruction in Environmental Sanitation 
at the University of California, Berkeley, Calif. This five -month course, 
commencing in January 1959, consists of full-time academic training in 
general sanitation, medical statistics, vector control, venereal disease 
control, bacteriology, and communicable diseases. Successful comple- 
tion leads to designation and assignment as Environmental Sanitation Officer. 

Applications must be submitted to the Chief, Bureau of Medicine and 
Surgery via the chain of command, to reach the Bureau no later than 15 
August 1958. The following information is required in each application: 

1. Statement of total service 

2. Resume of academic background 

3. Obligated Service Agreement (as set forth in 
paragraph 8a. of BuMed Instruction 1520. 12) 

It is highly desirable that a copy of all transcripts of formal college 
training be submitted with the application unless these have been furnished 
previously to the Bureau. Should the deadline of 15 August prevent sub- 
mission of transcripts to accompany the request, such transcripts may be 
forwarded as soon thereafter as practicable. Dispatch requests may be 
submitted if necessary to meet the deadline, but must be confirmed as 
soon as practicable with complete letter application. (MSC Div, BuMed) 

Medical News Letter, Vol, 32, No. 3 25 

MSC Training in Navy Management 

Early applications are desired from eligible Medical Service Corps 
officers interested in attending the Navy Management course convening in 
January 1959 at the U.S. Naval Postgraduate School, Monterey, Calif. 
This five -month course is designed to provide executive development educa- 
tion at the postgraduate level. While it is desirable that applicants hold a 
bachelor's degree from an accredited educational institution, this is not 
required. Two (2) officers of the Supply and Administration section have 
completed this school successfully, and it is planned to enter two (2) in 
each convening class (January and August) so long as quotas are available. 

Applications for this full-time in-service program must be submitted 
to the Bureau via the chain of command, and should be received no later 
than 15 August 1958 for favorable consideration. Eligibility requirements 
and application procedures are contained in BuMed Instruction 1520. 12. 
Dispatch requests may be submitted if necessary to meet the deadline, but 
must be confirmed as soon as practicable with complete letter application 
including the required obligated service agreement. (MSC Div, BuMed) 

T> Jjt «-j> Jp Jp. 3}C 

From the Note Book 

1. A recent directive authorizes the appointment of a civilian physician as 
deputy director of the Armed Forces Medical Publication Agency and assoc- 
iate editor of its publications. Applicants must be citizens of the United 
States; be graduates of approved medical schools in the United States or 
Canada; have completed a one-year accredited internship; have at least 

2 additional years of clinical experience, and a minimum of 5 years 
experience in medical editorial work. Full time residence in Washington, 
D. C. is also required. A Civil Service grade up to GS-15 with a salary 
range up to $13,970 has been established for the new position. Physicians 
interested in this position should make informal application to the Director, 
Armed Forces Medical Publications Agency, 2300 E. St., N. W. , Washington 
25, D.C. (A. F. M. P. A. ) 

2. The Secretary of the Navy has approved insignia for wear by personnel 
in pay grades E-8 (senior chief petty officer) and E-9 (master chief petty 
officer). Personnel in pay grade E-8 *ill wear a rating badge consisting 

of the present chief petty officer's rating badge with one star worn above the 
eagle's head. Personnel in pay grade E-9 will wear a rating badge consist- 
ing of the present chief petty officer's rating badge with two stars arranged 
horizontally above the eagle's wings. This change will be promulgated in 
a future change to U. S. Navy Uniform Regulations. (Navy Dept. Office of 

26 Medical News Letter, Vol. 32, No. 3 

3. Twenty-three prominent physicians, nurses, social workers, hospital 
administrators, and public health officials met in Roanoke, Va. , June 9-13, 
1958, at the invitation of the Public Health Service to consider organized 
home care programs in the United States. Citing the fact that there are 
now approximately 50 programs functioning in this country which provide 
coordinated health services to patients in their own homes, the group urged 
more widespread development and support of such community programs by 
Federal, State, and local health and welfare agencies; the health and health- 
related professions; and health insurance agencies. (PHS, HEW) 

4. Nitrate blood levels can be influenced by nitroglycerin or pentaerythritol 
tetranitrate (PETN). There is an abrupt rise and fall in nitrate blood levels 
following administration of each dose of PETN in tablet form. By combining 
PETN in timed- disintegration capsules, a more uniform release of the drug 
is obtained. PETN provides a uniform sustained release of the drug and a 
prophylactic effect for 10 to 12 hours 1 duration in the treatment of angina 
pectoris. (Circulation, June 1958; J. W. Berry, M. D. , T. C. Roach, M. D, ) 

5. The hemiplegic patient is capable of unrealized restoration from a phys- 
ical, mental, and social level. When an integrated plan of treatment involving 
medical, neurosurgical, physical, psychological, and vocational aspects is 
applied, at least 90% of hemiplegic brain-damaged patients are amenable to 
rehabilitation in its various goals. (Radiology, June 1958; M. K. Newman, 

M. D. , B. Jewett, M.S., G. Frampton, B. S. ) 

6. The outlook for patients with paralysis agitans is much brighter. There 
is a much wider and safer selection of drugs to combat the symptoms of 
idiopathic and arteriosclerotic cases. Surgical procedures are being 
applied with greater skill and better understanding and they harbor brighter 
prospects of relief to the patients. (J. A. M. A. , 5 July 1958, L.J. Doshay, 
M.D. ) 

7. Chronic nonspecific pneumonitis is a definite entity that can be diagnosed 
clinically and roentgenographs ally. The initial treatment should be med- 
ical. For those cases failing to respond to intensive medical therapy or 
that recur promptly when medical therapy is discontinued, pulmonary resec- 
tion becomes the treatment of choice. (Ann. Int. Med. , June 1958; vV. R. 
Deaton Jr. , M. D. ) 

8. A Public Health Service study among nearly 200,000 U. S. veterans shows 
a significantly higher death rate among regular tobacco smokers than among 
nonsmokers. The first report on the extensive and continuing statistical 
survey was made to the Seventh International Cancer Congress in London. 
The survey generally supports the findings of earlier studies demonstrating 

Medical News Letter, Vol. 32, No. 3 27 

a statistical relationship between death rates and smoking. The study did 
not include clinical or laboratory research. (PHS, HEW) 

9. There is no simple formula for management of rubella in pregnancy. 
All factors must be carefully considered and each case carefully evaluated 
on an individual basis. At the present time, the prevention of congenital 
malformation caused by rubella can best be achieved by deliberate expos- 
ure of young girls to the disease. In this manner, they may acquire a 
durable immunity that will protect them during their childbearing period. 
(New England J. Med., 3 July 1958; S. Krugman, M. D. , R. Ward, M. D. ) 

10. Nine ovarian carcinomas of presumed mesonephric origin are reported. 
These tumors are characterized by tubular structures which often resemble 
wolffian duct tubules. Branching dichotomous tubules may prove to be a 
prominent feature. These neoplasms are malignant and when they arise in 
the ovary, presage a grave prognosis should capsular invasion and adher- 
ence to adjacent structures be present. (Surg. Gynec. & Obst. , July 1958; 
S.Kay, M. D..R. H. Hoge, M. D. } 

11. The "flat top and V" pattern of the electrokymogram in chronic con- 
strictive pericarditis is discussed as well as the opinions expressed by 
various authors in regard to this finding. The findings obtained by analytic 
roentgen kymography in 16 cases of chronic constrictive pericarditis are 
reported. (Am. Heart J. , July 1958; A. JLaconi, Palermo, Italy) 

12. A technique for evaluating the effects of heart-valve surgery while 
an operation is in progress has been developed by a team of surgeons and 
cardiologists at the National Heart Institute. With this technique, direct 
measurements are made of the heart's output of blood and of differences in 
pressure on each side of abnormally narrowed, or "stenosed" valve open- 
ings just before and after these openings are surgically enlarged. The new 
technique allows a more precise and immediate evaluation of the results of 
heart valve surgery than has previously been possible with conventional 
techniques by which pressures and output of blood are measured before and 
after an operation, but not during the operation. (PHS, HEW) 

**fe * i jfe it 
*¥* T" *C "p nr 

Ristocetin - Effects and Side Effects 

During an 18-month period, 37 cases of staphylococcal pneumonia were 
encountered in a Naval Hospital. Treatment was complicated by the emer- 
gence of staphylococcal strains almost totally resistant to available anti- 
biotic agents. 


Medical News Letter, Vol. 32, No. 3 

Ristocetin became available early in this experience and was admin- 
istered to 17 patients, from nearly all of whom antibiotic resistant staphy- 
lococci were isolated. Two additional patients were given ristocetin during 
the moribund state. In all, there were three deaths in the entire series 
of 37 cases. It is the purpose of this communication to report the effec- 
tiveness of this new agent and to emphasize precautionary measures to be 
observed in its administration. 

The dosage for the majority of staphylococcal infections is 25 mg/Kg. 
daily. Because the antibiotic is excreted mainly via the kidneys, it should 
be administered with caution in patients with a renal impairment. In these 
cases, the antibiotic may accumulate in the body fluids with an increased 
likelihood of toxic effects. This restriction also applies to infants and 
patients aged more than 65. In these groups, it is recommended that the 
dosage should be reduced by 25 or 50%. 

Leukopenia and neutropenia have been reported as complications of 
ristocetin therapy. In all cases, there should be a frequent determination 
of blood count with particular reference to the total leukocytes and the per- 
centage of polymorph neutrophils. 

Method of administration . The drug was available in 500 mg. ampoule 
units, and the required amount was dissolved in 30-100 ml. of 5% glucose 
and administered over a period of 10 to 30 minutes in 2 to 4 divided doses. 
The solution was injected into the tubing of an intravenous infusion system 
(5% glucose). One hundred to two hundred ml. of glucose solution was 
flushed through the tubing at termination of drug injection. According to 
experience, this more rapid method of administration resulted in less local 

To minimize toxic side effects, careful attention to dosage and tech- 
nique of administration is mandatory. Effects on the hematopoietic system 
are not common, but are more likely to occur when dosage exceeds 25 mg.Kg 
per day. 

Blood counts — with particular attention to the white blood cells and 
platelets — are recommended on alternate days during therapy. Depression 
of the white cell count should call for a reduction in dosage, or withdrawal 
of therapy in severe cases. 

Because ristocetin is excreted by the kidney, renal integrity should 
be appraised in every instance. Patients with renal impairment, the very 
old, and the very young should all receive a reduced dosage. 

With observance of the foregoing precautions, ristocetin has served 
as a safe and potent anti -Staphylococcal agent. (Captain G. L. Calvy MC 
USN, Lieutenant L. R. Schumacher MC USN, U.S. Naval Hospital, St. Albans, 
N. Y. ) 

(Refer to Medical News Letter, Vol. 31, No. 4, Page 13) 


Medical News Letter, Vol. 32, No, 3 




Erroneous Submission of Supplement 
to Dental Service Report 

Some dental activities have erroneously submitted the Equipment and 
Facilities Supplement to the Dental Service Report (DD-477-1) for the period 
ending 30 June 1958. 

Attention is invited to Article 6-150 (3) (b), Chapter 6 (Revised), 
Manual of the Medical Department, which states that the DD 477-1 shall be 
submitted as of January 1 each year. Submission as of July 1 is not re- 

sjc sfe # $ j|e s^ 

Casualty Treatment Training to be 
Exhibited in Brussels 

Captain V. J. Niiranen DC USN, Head, Training Aids Department, 
U. S. Naval Dental School, National Naval Medical Center, Bethesda, Md. , 
will monitor the U.S. Navy "Casualty Treatment Training Program" ex- 
hibit at the Federation Dentaire Internationale in Brussels, Belgium, during 
August 28 to September 3, 1958. 

* * * 


Credit for Attending Professional Meetings 

The Chief of Naval Personnel has authorized retirement point credit 
for each of the below listed professional meetings and symposium to be con- 
ducted on the dates listed. Eligible Naval Reserve Medical Department 
officers must register with the military representative present. Security 
clearance is not required. 

30 Medical News Letter, Vol. 32, No. 3 

Annual Meeting, American Psychological Association. Hotel Statler, 
Washington, D. C. , 26 August - 3 September 1958 

This meeting, having military significance for those inactive Reserve 
Medical Department officers whose specialty is psychology, will present 
lectures and discussions which will provide information and techniques 
employed in psychology that are not readily available to these officers 
in their civilian pursuits, but invaluable to their respective functions 
in the event of mobilization. 

Fourth Naval District Ninth Annual Military Medico-Dental Symposium, 
U.S. Naval Hospital, Philadelphia, Pa., 22 - 24 October 1958. 

Under the sponsorship of the Commandant, Fourth Naval District, 
this symposium has as its theme "Space Medicine" and will be presented 
by speakers and discussants of outstanding prominence in their specialties. 
Addresses will be given by the Honorable Frank Berry, Assistant Secre- 
tary of Defense (Health and Medical) and Doctor Aernher von Braunn, 
Director, Development Operations, Army Ballistics Missile Agency, 
Redstone Arsenal, Huntsville, Ala. This symposium is presented for 
the benefit of Medical Department personnel of the Armed Services, both 
active and inactive, 

65th Annual Convention of the Association of Military Surgeons, Hotel 
Statler, Washington, D."'C." 17 '-" 19 November 1958. 

The theme of this meeting is "Dynamic Medicine and Rehabilitation 
in the Space Age" and will present subjects which will afford those in 
attendance an excellent opportunity to remain abreast of the latest devel- 
opments in military medicine. The Assistant Secretary of Defense 
(Health and Medical) has endorsed this convention as suitable training 
for inactive Reserve Medical Department officers of the Armed Services. 


Medical Ensign USNR Designator Changed 

Formerly known as Ensign 1995 (Medical) officers, undergraduate 
medical students holding commissions in the Navy's Ensign Medical Prog- 
ram now have a new designator - "1915. » This change contained in BuPers 
Instruction 1210. 4B of 31 May 1958 also provides a new designator for den- 
tal students - "1925, " and theological students - "1945. " Prior to 31 May 
1958, student officers in medical, dental, and theological schools were 
assigned the numerical designator 1995 followed by their particular staff 
corps title. 

ifr itt nftf jflf jfc A 

Medical News Letter, Vol. 32, No. 3 


Contingency Option Act and Aid to Dependents 

If you are nearing completion of 18 years' service creditable for 
basic pay, you may want to take a look at the provision of the "Uniformed 
Services Contingency Option Act. " 

This Act which applies to Reserve and Regular officers and enlisted 
personnel allows you to provide an income for your survivors by electing 
to receive a reduced amount of retired pay. In this manner, you may pro- 
vide an annuity equal to one-half, one-fourth, or one-eighth of the reduced 
amount of retired pay. The Act provides for four types of annuities. 

If you want to provide this benefit for your survivors, you must make 
the election before you complete 18 years of service for basic pay purposes. 
These 18 years, therefore, are not limited to "years of satisfactory Federal 
service. " 

Complete information on the Act may be found in BuPers Instruction 
1750. 2. In addition, Reservists may obtain a booklet, Percentage Cost 
Tables for Selection of Options under the Uniformed Services Contingency 
Option Act of 1953, NavPers 15866, from their District Publications and 
Printing Office at no cost. (The Naval Reservist, June 1958) 

?F SfC Jjc ?je ?Jc 3$E 


The Seventeenth Veterans Administration- Armed 
F orces Conference on Chemotherapy 
of Tuberculosis 

Twelve years ago, when streptomycin first became available for the 
treatment of tuberculosis in man, a nationwide cooperative study group 
was formed of Veterans Administration (VA) tuberculosis hospitals using 
this antibiotic. Its purpose was to learn, while this powerful newly dis- 
covered antituberculous agent was being used, about dosage, therapeutic 
effect, toxicity, and the best methods and optimum duration of its admin- 
istration. The present cooperative study group with interests in all phases 

32 Medical News Letter, Vol. 32, No. 3 

of chemotherapy of tuberculosis includes 56 VA hospitals and 4 hospitals 
from the three branches of the Armed Forces. Participation as a study- 
unit is entirely voluntary as is cooperation in any or all of the individual 
studies. A cooperation unit by volunteering to engage in a particular study 
agrees to treat all suitable patients by a certain regimen or to allocate 
them randomly between certain mutually agreed-upon regimens. Random- 
ization is effected by a sealed-envelop system. All cases are reported 
on standardized forms from which data are transferred to IBM cards and 
tabulated to provide maximum information. Annually (usually in February), 
representatives from the study units meet to discuss the results of the 
previous year's work and to plan projects for the following year. The 1958 
meeting — the seventeenth of these conferences — was held in Memphis, Tenn. , 
February 3-6, 1958. Attendants and participants included 100 VA represen- 
tatives, some 350 physicians and scientists, and a number of distinguished 
visitors from abroad, perhaps the most significant of whom were two repre- 
sentatives of the British Medical Research Council who acted as official 
liaison between the two tuberculosis research groups on either side of the 
Atlantic . 

Various related papers, discussions, and future cooperative plans are 
summarized under 16 appropriate headings to provide in brief the results 
of this Conference. 

STREPTOMYCIN administered daily combined with isoniazid and with 
isoniazid and para-aminosalicylic acid (PAS) was evaluated by the study 
units during the past 2 years. General regimens had been designed to ans- 
wer the following questions: "In patients with no prior chemotherapy, what 
is the comparable therapeutic efficacy of daily streptomycin and isoniazid 
as compared with isoniazid combined with PAS?" and secondly, "Does the 
addition of a third drug (daily streptomycin in combination with both ison- 
iazid and PAS) contribute anything to the therapeutic efficacy, also consid- 
ering factors of toxicity and emergence of resistance?" During this interval 
over 1000 cases of pulmonary tuberculosis had been randomly allocated 
among 3 regimens: streptomycin, 1 gm. daily, combined with isoniazid, 
300 mg. daily; isoniazid, 300 mg. daily combined with PAS, 12 gm. daily; 
and all 3 drugs in these dosage schedules. The groups were approximately 
equal in number and the patients in each group showed similarity in such 
background factors as age, degree of disease, and size and number of 
cavities. Therapeutic results were also very similar in more than 600 
patients who had been treated for periods long enough for evaluation. These 
results were measured in such terms as x-ray improvement, disappear- 
ance of tubercle bacilli from sputum or gastric contents (proved by culture), 
and closure of cavities of varied sizes. Various inter-regimen differences 
were not significant when evaluated at 4 -month or 8 -month end points. 

Bacterial resistance was slight (of those with positive sputum, bacilli 
were fully resistant in 3 to 4%and partially resistantin 6 to 9%), and identical 

Medical News Letter, Vol. 32, No. 3 33 

in the 3 regimens. Toxicity was least with isoniazid and greatest in the 
'triple -drug" regimen — 7% had to stop PAS and 14% had to stop streptomy- 
cin. From these results, one might conclude that in all probability triple - 
drug therapy, even with daily streptomycin, had no special value from the 
therapeutic standpoint or from the standpoint of the prevention of bacterial 
resistance, and that this regimen had the drawbacks of greatest toxicity, 
greatest difficulty in administration, least suitability for outpatient treat- 
ment, and greatest danger of multiple-drug sensitization. Daily strepto- 
mycin seemed not to be superior to daily PAS as a companion drug to 
isoniazid. It was suggested that triple-drug therapy might find its great- 
est usefulness in the early treatment of a patient who had had previous drug 
therapy and who might have bacteria partially resistant to one or more of 
the three drugs. The study units decided to continue these regimens for a 
further brief period to obtain for treatment a sufficient number of the most 
critical cases — those with large cavities — and thus to give solid statistical 
significance to the absence or presence of inter-regimen differences. The 
daily use of streptomycin was associated with a moderate amount of damage 
to the eighth cranial nerve, especially noted in men past the age of fifty, 
necessitating discontinuation of the drug. Several studies in which dihy- 
drostreptomycin pantothenate was tested against dihydrostreptomycin sul- 
fate gave somewhat contradictory results. Two of these were reported 
as showing no indication that this new preparation was less ototoxic. Two 
other studies indicated that it might be less toxic. In discussion, strep- 
toduocin was reported as being less ototoxic when used daily than either 
streptomycin or dihydrostreptomycin. 

ISONIAZID has established itself as the most powerful agent in the 
treatment of tuberculosis and as an almost indispensable senior partner 
in all combined regimens; however, many questions still remain to be 
answered about its most efficient use. Previous evidence suggested that 
isoniazid alone might be an effective agent for the treatment of lesions of 
tuberculosis in which there is a minimum of tissue destruction and, there- 
fore, the likelihood of the emergence of resistant bacilli is slight. Accord- 
ingly, the study units have been randomly distributing minimal cases and 
moderately advanced noncavitary cases between isoniazid alone (300 mg. 
daily} and in combination with PAS. The results to date in 150 cases re- 
ported upon reveal that x-ray improvement, sputum "conversion, " and 
achievement of the "target point" occurred equally often in both groups. 
In addition, isoniazid alone was better tolerated and because only one 
patient in each group shed isoniazid-resistant bacilli it did not seem infer- 
ior in this respect. Thus encouraged, the study units voted to enlarge this 
randomized study and to make similar investigation of patients with tubercu- 
lous pleural effusions. 

At the other end of the spectrum, two reports were presented to indi- 
cate that larger doses of isoniazid (10 to 18 mg. per kilogram of body weight) 

34 Medical News Letter, Vol. 32, No. 3 

with PAS (and. pyridoxine or vitamin B& to prevent peripheral neuropathy) 
or high isoniazid dosage with daily streptomycin (with or without PAS) may 
be more effective than the commonly used doses of 4 or 5 mg. per kilogram. 
With high isoniazid regimens, sputum conversion was generally reported as 
being over 95%. Other evidences of improvement were impressive, al- 
though many cavities remained open. To date, however, no randomized 
studies have been done comparing the two isoniazid dosage levels. There 
was no INH (isonicotinic hydrazide) toxicity when pyridoxine (50 to 100 mg. 
daily) was administered. Spurred on by these favorable results, the study 
units plan to evaluate regimens in which "high" and "low" isoniazid dosage 
schedules will be the major variable with PAS as the companion drug. 

The subject of isoniazid-resistant bacilli is of great interest because 
of the generally lowered virulence of this variant in animal experiments and 
perhaps for human beings. That it is virulent for man cannot be questioned; 
however, 1 or 2% of all newly infected persons who have never had treat- 
ment with this drug shed resistant bacilli, and by far the greatest likelihood 
exists that these infections were incurred by contact with persons in whom 
resistant bacilli developed as a result of previous isoniazid therapy. Studies 
with resistant bacilli in monkeys indicate that occasional isoniazid- sensitive 
mutants — with correspondingly high virulence — may develop in animals 1 
lungs, revealing the possible mechanism of the development of resistant 
strains in human beings under isoniazid therapy. 

CYCLOSERINE used alone proved to be a rather weak but, neverthe- 
less, effective agent. A regimen containing isoniazid, 300 mg. and cyclo- 
serine, 500 mg. , (in 309 patients, all with cavity formation) was compared 
by randomization with isoniazid in combination with PAS. Although good 
results were obtained from both combinations, patients receiving isoniazid 
combined with PAS had less evidence of x-ray worsening. This was cal- 
culated as a "risk" of 12% in 8 months in the isoniazid-cycloserine group as 
compared with only 1% in the others By other criteria (cavity closure, 
sputum conversion, and the development of isoniazid-resistant bacilli) the 
group receiving the combination with PAS showed slight but consistent 
superiority. With the 500 mg. daily dosage of cycloserine (250 mg. twice 
a day) no convulsions were noted; therapy was discontinued in one case 
because of optic neuritis and in two because of emotional or neuropsychia- 
tric upsets. PAS toxicity caused three times as many patients to be dropped 
from the study as cycloserine toxicity. Two brief reports indicated that 
cycloserine, alone or with viomycin, could be of value in an occasional 
patient with advanced disease who had failed to respond or who had relapsed 
after months or years of treatment with more generally used drug regimens. 
Experiences with hospitalized psychiatric patients proved that — contrary 
to earlier recommendations — the mental condition is not a contraindication 
to, nor is it made worse by, the use of cycloserine. 

Medical News Letter, Vol. 32, No. 3 35 

PYRAZINAMIDE and isoniazid, 300 mg. , were combined in regimens 
(one with a 3 gm. dose of pyrazinamide and one with a 1. 5 gm. dose) for 
comparison with the combination of isoniazid and PAS. All patients includ- 
ed had cavitary cases. In terms of therapeutic effect, the combinations 
of isoniazid with PAS and with 3 gm. of pyrazinamide were approximately 
equal, but hepatotoxicity (which occurred in 10% and consisted chiefly in 
abnormal liver -function tests) was a disturbing factor in the pyrazinamide 
group. When the daily dosage of pyrazinamide was cut from 3 to 1. 5 gm. 
and evaluated in a smaller group of patients, the therapeutic effect was 
about the same, but toxicity was only one -third as great. It is believed 
that the results warranted a more extensive evaluation of 1. 5 gm. of pyra- 
zinamide as a companion drug to isoniazid and plan to randomize cavitary 
cases between this regimen and isoniazid combined with PAS. 

PARA-AMINOSALICYLIC ACID, acting together with isoniazid, has a 
powerful antituberculous effect; no other regimen has been shown to be con- 
sistently superior in terms of lowered bacterial resistance, cavity closure, 
or conversion of sputum bacteriology. Problems of particular interest 
centered upon gastrointestinal toxicity and the use of a single dose of 6 gm. 
daily rather than 12 gm. in divided dosage. In guinea pigs, a single daily 
dose was found as effective as the same daily amount divided into 2 doses; 
two single doses were as effective as 10 to 12 times as much given in the 
diet. In the treatment of a group of patients, when a single daily dose of 
PAS (approximately 6 gm. ) was combined with streptomycin or isoniazid, 
therapeutic results were equal to those with larger total (but divided) daily 
doses, bacterial resistance was slight and drug tolerance was superior. 
No uniform superiority in PAS tolerance could be demonstrated when com- 
parisons were made between sodium, potassium, or calcium PAS and 
Rezipas — patients were found with gastrointestinal intolerance to each of 
these, but could take some other preparation. There seemed to be no re- 
lation between the tolerance and the blood levels or free -acid equivalent. 
Least over all intolerance was obtained with one daily dose of 6 gm. of 
Rezipas. Evaluation of streptomycin will be continued twice weekly using 
sodium PAS in two dosage schedules of 12 gm. daily (divided into 3 doses) 
and 6 gm. in a single dose. 

STREPTOVARICIN, an antibiotic, was used for the retreatment of 
patients revealing cavitation and tubercle bacilli susceptible to isoniazid. 
The daily dose was 3 gm. orally in a single dose with isoniazid, 100 mg. , 
three times a day. Of 26 patients reported, 10 became isoniazid resistant 
at the end of 4 months and the therapeutic effects were considered equal to 
those of isoniazid alone. Such symptoms as lethargy, anorexia, and nausea 
caused considerable difficulty. No further study of this drug is planned. 

36 Medical News Letter, Vol. 32, No. 3 

THIOCARBANIDIN is tuberculostatic; its action appears to be of the 
same order as that of PAS, but is apparently produced in vivo in much 
smaller doses. In guinea pigs, it was definitely effective in prolonging the 
lives of animals and in lessening the amount of tuberculosis that did develop, 
but much less so than effective amounts of streptomycin or isoniazid. It 
appeared to reinforce the effects of small doses of streptomycin. Resistance 
to it was developed (in vitro) and the organisms then revealed cross resis- 
tance with amithiozone (TBi, tibione). When used in 16 patients (as Thioban) 
in dosages of 0.25 gm. twice a day to 0. 5 gm. four times a day, there were 
no evidences of toxicity to the bone marrow, kidney, thyroid gland, or liver. 
Therapeutic effects could not be evaluated adequately and further study of 
this drug is planned. At present, its most suggestive use is perhaps as an 
alternative drug for PAS in combined chemotherapy, but there is far too 
little experience with it at present for even a tentative appraisal of its future 

KANAMYCIN, a new antibiotic, appeared to be less effective in guinea 
pigs than streptomycin with which, however, it demonstrated appreciable 
additive (or synergistic) effect. Used intramuscularly (absorption via the 
oral route being slight) it was not toxic for guinea pigs, but revealed some 
renal toxicity in human beings. High bacterial resistance developed in vitro 
after but four transfers and crossresistance to neomycin was observed. Its 
toxicity for guinea pigs, however, was insignificant compared to that of neo- 
mycin. Further evaluation of kanamycin is planned. 

Photochromogenic Pathogens 

Further reports were made on infections with acid-fast (but not clearly 
Mycobacterium tuberculosis) bacilli. Infections with photochromogenic bac- 
teria (which become pigmented deep yellow or orange when growth continues 
after exposure to light) are especially common in the Middle West, and non- 
photochromogenic "atypical" or "anonymous" infections are especially com- 
mon in the Southeast. These photochromogenic bacilli all show certain 
characteristics: a negative Konno niazin test, growth in room temperature 
high pretreatment resistance to PAS, isoniazid, and streptomycin, especi- 
ally to PAS, and guinea pig virulence. Forty-nine cases due to this organism 
were reported from Cook County, 111. During a 3-year period, of 929 "posi- 
tive" cultures for tubercle bacilli, 32% were atypical; in 49 patients, photo- 
chromogens were the only bacilli recovered and they were believed to be 
the cause of the pulmonary disease noted. These cases were heavily con- 
centrated in 3 contiguous communities in a small area west of Chicago that 
contributed 63% of the photochromogenic cases, although only 19% of the 
cases of tuberculosis. There were no evidences of intrafamily contagion; 
indeed, family contacts had a low prevalence of tuberculin reactors. The 
lesions tended to be fibrotic and fibrocavitary ; exudative, caseous, acute 

Medical News Letter, Vol. 32, No. 3 37 

inflammatory or extrapulmonary manifestations were not observed. The 
organisms showed high resistance to PAS and moderate resistance to strep- 
tomycin and isoniazid. Response was slow to treatment with high isoniazid 
dosage, and surgical complications with resection were very frequent (40% 
as compared to 9% in typical tuberculosis). The exact nature of this dis- 
ease or of these bacilli is not known. The adjective "anonymous" was sug- 
gested as preferable to "atypical" which implies that these are a variant 
of some "typical" organism, such as Myco. tuberculosis, and present 
information suggests that they are not. 

I nfection with Resistant Tubercle Bacilli 

At the 1957 conference, 4 studies were analyzed to reveal that appar- 
ently about 2% of all patients with untreated tuberculosis will have organisms 
reported as resistant to isoniazid or streptomycin. This still obtained with 
some variations, but with no appreciable annual increase. These conclusions 
were drawn from 3 separate reports involving approximately 8000 cases in 
the United States and 1000 in Great Britain, Just how many of these infec- 
tions were due to contagion previously treated, but still infectious cases, is 
not known. It was suggested that completely new — primary — cases should 
be carefully analyzed for possible evidence of an increasing rate of infection 
with resistant bacteria. 

Follow -Up Studies 

In the prechemotherapy years, the relapse rate of tuberculosis was 
high in cases classified as "arrested" by National Tuberculosis Association 
(NTA) standards. Several papers described follow-up studies in a large 
number of patients treated by chemotherapy with and without thoracic sur- 
gery. Some 900 patients followed for 3 years after discharge as "arrested" 
or "inactive" from a VA Hospital revealed that, of those discharged between 
1947 and 1952, 30% relapsed; in the next 2 years, this figure dropped to 14% 
concomitant with the introduction of isoniazid and of continuing outpatient 
treatment. Most of the relapses responded well to a second course of chemo- 
therapy. Of 2500 patients discharged from an Army Hospital from 1951 to 1956 
and followed for 1 to 5 years, only 4% relapsed. Two hundred and twenty-six 
patients with pulmonary resection at another VA Hospital followed for 1 to 7 
years (145 for 3 years or longer) revealed 8 relapses (3. 5%), only 2 while 
the patients were still on drug therapy. Patients with open cavity and positive 
sputum at the time of surgery had a 7. 5% relapse rate (chiefly in patients 
with drug -resistant bacteria). All relapses occurred in patients who had 
active disease with caseation in the removed specimen and in whom residual 
disease was to be expected on the basis of the preoperative x-ray study. All 
reactivation of the disease occurred at, or near, the site of preexisting dis- 

38 Medical News Letter, Vol. 32, No. 3 

Thoracic Surgery 

Combined with chemotherapy, surgical collapse and resection were 
performed in many patients. A series of 142 thoracoplasties done between 
1946 and 1950 revealed 62% successes at the end of one year with a gradual 
increase in relapses so that 7 to 1 1 years after operation, 44% of patients 
were well and 10% were dead of tuberculosis or pulmonary insufficiency— 
the larger the cavity, the worse the result. In a recent series, 1951 to 
1955, the results were found to be even worse because these were generally 
the "salvage" patients who had resistant bacilli, could not withstand resec- 
tional surgery, et cetera. In the "open-negative" cases, thoracoplasty 
was effective (in 86%) as a definitive surgical measure. The use of extra- 
periosteal collapse with Lucite spheres or Ivalon sponge plombage was 
reported as an effective collapse measure for cavitary disease where a 
cavity of moderate size is located high in the lung field. It is indicated in 
older patients with limited pulmonary reserve and in bilateral disease when 
bilateral resection is thought to be too hazardous. This form of collapse 
appeared to be effective in many cases that did not seem amenable to other 
surgical measures; resection was quite feasible later in many of the failures. 
In the absence of infection, the plomb was generally left in permanently; 
however, considerable difference of opinion and experience exist as to its 

Analysis was made of the surgical experiences of 44 hospitals contri- 
buting statistics to the Conference, Some 1300 cases of excisional surgery 
were reported and comparisons were made with previous years. These indi- 
cated a decrease in segmental and subsegmental resections with no change 
in pneumonectomies and some increase in lobectomies. Bronchopleural 
fistula — by far the most serious and frequent complication — occurred in 
14% after pneumonectomy, 7% after lobectomy, and 4% after segmental 
surgery. Surgical death rates were 15% after pneumonectomy, 4% after 
lobectomy, and less than 1% after segmental surgery. When the risk of 
pulmonary resection was correlated with preoperative sputum status, it 
was found that the risk of empyema and of postoperative death after lobec- 
tomy and pneumonectomy was appreciably higher in the sputum -positive 
group. This did not hold in segmental reactions. The opinion was expressed 
that resistant bacilli and copious sputum added to this hazard. Active tuber- 
culosis after resection was attributed to residual nonresected lesions, resid- 
ual bronchiectasis, bronchopleural fistulas, sutures in the bronchi, wound 
infections, and in 33% there were no obvious causes. The majority of "fail- 
ures" became inactive with further drug therapy or further surgery. Of 
2326 resected cases, 90% of the patients who had but one resection were 
well; when a later contralateral resection was needed, only 50% were well. 
The late reactivation rate was 6 to 9%; preoperative duration of drug therapy 
had no noticeable effect upon this late relapse. 

Medical News Letter, Vol. 32, No, 3 39 

Corticosteroid Therapy 

Much discussion about this subject revealed that the steroids are 
beneficial when used in ample dosage for seriously ill patients with tuber- 
culosis, whether meningeal or otherwise. If effective antituberculous drugs 
are also used and the steroids tapered off rather than stopped abruptly, this 
is believed to be safe in all cases and perhaps life-saving in many. A pre- 
liminary, report was made of a British Medical Eesearch Council project 
(begun in October 1957) in which all included patients with pulmonary tuber- 
culosis will receive streptomycin, PAS, and isoniazid; in addition, in a 
double blind study, one-third will receive ACTH for 3 months and one- 
third will receive prednisone; the remainder will serve as controls. The 
study units recommended no general steroid study, but will volunteer in- 
dividual research designs to evaluate this problem. 

Duration of Chemotherapy 

Patients are being randomized after reaching the "target point" 
(sputum conversion, cavity closure, and stable x-ray appearance) between 
two regimens: chemotherapy (any effective drugs) for an additional 9 months, 
and chemotherapy for an additional 18 months. As yet, this study has not been 
in existence long enough for evaluation. Its purpose is to determine what ben- 
efit, if any, upon relapse rates chemotherapy provides when continued well 
beyond the point of inactivity (according to NT A standards). 

Fungous Infection 

Of much interest were several reports on amphotericin B. In the treat- 
ment of cryptococcal meningitis, 7 of 9 patients are alive and 6 have nega- 
tive spinal fluid cultures. This drug has also been used in coccidioidal 
meningitis with early promising results. Serologic surveys for histoplasmosis 
have revealed a very large percentage of positive reactors in tuberculosis 
hospitals, especially in the endemic areas. Such tests have helped in the 
detection of new cases and in the diagnosis of pulmonary problems. Special 
cooperative study groups now exist for blastomycosis, histoplasmosis, and 
coccidioidomycosis; in the last of these, an evaluation is planned of ampho- 
tericin in the disseminated and meningeal forms. This drug is to be evaluated 
as well in histoplasmosis on a randomized basis. 

Pleural Effusions 

The value of thoracotomy in the diagnosis of pleural effusions was re- 
ported in a study from an Army Hospital. In 38 cases of proved tuberculosis, 
pleural biopsy alone revealed nonspecific fibrosis in 5, whereas the lung 
revealed tuberculous changes. In 18 cases, in which the tuberculin test was 
positive, thoracotomy gave no evidence of tuberculosis. Although these 
patients may have tuberculosis, they are being observed without therapy on 
the basis of the negative biopsy, (Rothstein, E. , The Seventeenth Veterans Admin- 
istration-Armed Forces Conference on the Chemotherapy of Tuberculosis : New 
England J. Med., 2_58: 1199-1204, June 12, 1958) 

MJ. S. GOVERNMENT P1UKTIM0 OFFICE : 1958 O ■ 481495 


Medical News Letter, Vol. 32, No. 3 


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